OncoMedia Sep-Dec 2015

Vol 1 | Issue 2 | Sep – Dec 2015 | page:34-35 | Dr Ashish Gulia & Dr Ashok Shyam

Author: Dr Ashish Gulia[1] & Dr Ashok Shyam[2, 3]

Dr. Ashish Gulia MS (Ortho), Mch – Surgical Oncology
[1] Fellowship – Musculoskeletal Oncology (TMH – HBNI)
Asst. Professor – Orthopaedic Oncology, Tata Memorial Hospital, Mumbai, India.

Dr Ashok Shyam MS (Ortho)
[2]Indian Orthopaedic Research Group, Thane, India
[3] Sancheti Institute for Orthopaedics &Rehabilitation, Pune, India

ONCOMEDIA will focus on News and Event related to Bone and Soft Tissue Tumors from all across the World. Specific focus will be Industry updares,New Research, Social Impactof tumors, Basic Scinece and developmentsin cytogentics and allied fields. In short OncoMedia is a place for most interesting read in this entire issue 🙂

Bone Tumors on You tube

You tube has revolutionised the information dissemination scenario. From reading text the scenario has now changed of visuals. Medical knowledge dissemination through you tube is started almost from the inceptino of the website. There are many videos and essential details that are available on the you tube website. The problem is selecting a few and finding time to watch them. The JBST Oncomedia team and gone through you tube and found some interesting vedioes that we can recommend to our readers. We will also be psoting links of these videos on jbstjournal.com too. Lets see some details of these videos.
1. Pathology of Bone tumors. Essentially meant for postgraduate students, this video gives pictures of true specimens and their description.


Link: https://www.youtube.com/watch?v=oHfozp2e8zg 

2. Bone Tumor Imaging: is a video of powerpoint lecture by Dr K L Verstraete. Although made in 2012, the lecture is quite informative and will help many to update their knowledge about Bone Tumor imaging.


Link: https://www.youtube.com/watch?v=EsLIUyExEXU

 

 

3. KOC Radiology conference: This KOC talk was given by our editorial board member Dr Bhavin Jhankaria in 2014. This is a very thorough update on imaging of bone tumor and delivered in inimitable style of Dr Bhavin. We highly recommend everyone to watch this video.


Link: https://www.youtube.com/watch?v=g2TGHrYGAvA

 

 

4. MSK Imaging bone tumor: Finally we can complete the update on bone imaging by watching this detailed video. Again presented in format of voice over of a powerpoint presentation, this includes a very good visual appeal to the video.


Link: https://www.youtube.com/watch?v=VcYRoB-qRX0

We will be providing reviews of some more youtube resources in the next issue of Oncomedia. Please provide us with your comments, suggestions and criticism for this feature of JBST.

 

Orthopaedic Powerpoints is a new presentation of the Orthopaedic Research Group. Although PPT’s are readily available online but many of them are not recent or with medicore content. At OrthoPowerpoints.com we will assure that best quality of material is published and circulated. The website will feature peer reviewed powerpoints and to begin with includes members by invitation only. Few presentations from the editorial board of JBST are available online. Visit www.orthopowerpoints.com for more details.

IMSOS 2016:The second Annual conference of Indian Musculoskeletal Oncology Society is planned on 11-13 March 2016 and will be held in Kochi. Visit the website www.imsos2016.org for more details.

Invitation (1)
IMSOS – Surgeon’s Training Initiative: This will be a travelling fellowship open only to IMSOS members allowing them a 6-8 weeks fellowship at a centre of their choosing. Two fellowships per year will be available. Interested readers can join IMSOS and look for further announcements

 

           Dr. Ashish Gulia
 Dr. Ashok Shyam

(Abstract)      (Full Text HTML)      (Download PDF)

Role of Image Guided Interventions in Orthopaedic Oncology

Vol 1 | Issue 2 | Sep – Dec 2015 | page:25-29 | Himanshu Pendse[1*], Aniruddha Kulkarni[2], Manish Agarwal[2]

Author: Himanshu Pendse[1*], Aniruddha Kulkarni[2], Manish Agarwal[2]

[1]P.D Hinduja Hospital Veer Savarkar Marg, Mahim, Mumbai, India

Address of Correspondence
Dr. Himanshu Pendse
P.D Hinduja Hospital Veer Savarkar Marg, Mahim, Mumbai, India.
Email: himanshu.pendse@gmail.com

Abstract

Interventional radiology has grown in leaps and bounds specifically in field of orthopaedic oncology. The procedures have advantage of being minimally invasive and have a much better postprocedure rehabilitation. These procedures can be broadly classified as Non-vascular and Vascular interventions. Common non-vascular procedures comprise of image guided biopsies, radiofrequency ablations, vertebroplasty and khyphoplasty. Vascular procedures comprise of Embolotherapy and Sclerotherapy. Isolated Limb Infusion (ILI), MR-HIFU (MRI-guided High Intensity Focused Ultrasound), Cryoablation are few of the more recent advances in the field of interventional radiology. Each procedure has its own indications, contraindications and safety profile. The current article provides an overview of these procedures and there clinical importance.
Keywords: Interventional radiology, orthopaedic oncology.

Introduction

Image guided interventions or otherwise popular as the field of interventional radiology comprise of procedures which are performed with the help of an imaging modality such as fluoroscopy, USG, CT or MRI. With the rising preference for minimal invasive therapies, these procedures enjoy an increasing scope in the patient management. Other than elective procedures, interventional radiology proves invaluable for managing medical and surgical emergencies. In recent years, interventional radiology is playing a vital role in the field of orthopedics and orthopedic oncology. This article will give an outline of the common procedures performed by an interventional radiologist in orthopedic oncology. These procedures can be broadly classified as Non-vascular and Vascular interventions.

Fig 1 2

Non-Vascular Interventions
Common non-vascular procedures comprise of image guided biopsies, radiofrequency ablations, vertebroplasty and khyphoplasty.
Image guided biopsies and fine needle aspiration cytology (Fig 1A and B, 2A and B, 3A and B and Fig 4):
This is emerged as a safe, faster and accurate tool for getting a diagnosis from a musculoskeletal lesion. It has safer and has better patient tolerance as compared to conventional open biopsy [1].

Fig 3 4

Indications
1. Determine whether lesion is benign or malignant
2. Obtain material for microbiological examination in a suspected infective lesion
3. Determine status of a lesion in a patient with known primary
Contraindications:
Known coagulopathy, Pregnancy (for CT-guided procedures)

Fig 5

Special considerations
It is imperative to determine a safe route for biopsy, which comes in the excision and/or radiation field for treating the primary lesion. Classic “no-touch” lesions like myositis ossificans in evolving stage; subchondral geodes etc should be identified on imaging and prevented from being biopsied. These lesions appear aggressive on histology, causing radiological and pathological discrepancies.

Fig 6

Equipment and Techniques
Fluoroscopy, USG, CT or MRI have been used for image guidance for a biopsy. CT scan is most often used for biopsy of bone lesions [2]. The main advantage of CT being precise visualization of trajectory of the needle. thus preventing damage to the important structures like the neurovascular bundle.
USG is preferred for superficial bone lesions with a targetable soft tissue component. It is preferred in patients where radiation exposure has to be avoided [3].

Fig 7

Fluoroscopy is a good modality for biopsy of large lesions. In some cases, the lesion is visible only on MRI. In such cases, MRI-guided biopsy is indicated.
The procedure is generally performed under local anaesthesia with light sedation when necessary. The patient lies prone for vertebral biopsy. For any other bone, the position depends on the site of the lesion. Compartmental anatomy greatly influences the needle approach, and such knowledge is critical for preventing unnecessary surgery and loss of limb function. It is important to stress that the biopsy trajectory should be through the tissues that would be excised or comes in the radiation field to prevent recurrence along the biopsy tract.

Fig 8
Generally, an 11-15G Trephine Bone Biopsy Needle is used to target bone lesions without significant soft tissue component. For a FNAC, a 22 G needle is generally used. The yield is better for a larger needle. In case of vertebral biopsy of the dorsal vertebrae, it is advisable to use a 13G needle instead of an 11G needle due to the thinner pedicles of the dorsal vertebrae. In lesions with a significant soft tissue component, an 18G co-axial biopsy set with a co-axial needle and a semi-automated or automated gun would be a good choice. In a circumscribed lytic lesion, it is prudent to use an 11/13G bone biopsy needle as an anchor. Through this, the 18G biopsy needle is passed to obtain soft tissue cores. MRI guided biopsies need special MRI compatible needles. Sampling should be performed by fine-needle aspiration (FNA) along with Core Needle Biopsy as many interventional radiologists feel that both the techniques have a complementary role.

Fig 9

Complications
Pain, bleeding, infection, biopsy tract recurrence and bone fracture are the common complications. Instilling gelfoam torpedos in the biopsy tract can arrest bleeding from biopsy of hypervascular metastasis. Post-procedural Care: Patient may be advised to take painkillers if pain is significant Antibiotic cover is not necessary post-biopsy. Biopsy Yield and Outcomes: This is an important issue for bone biopsies. It is important to take enough samples, especially when benign disease is suspected. Several studies have shown higher accuracy of core needle biopsy (89.7%-96%) to fine needle aspiration cytology (64%-88%) [4]. Biopsy of bone lesions with soft-tissue components (93%, 89%) has higher diagnostic accuracy than biopsy of lytic lesions (85%, 71%) [5]. Also, in case of cystic lesions, biopsy from the wall of the cystic lesion has better yield than aspirating fluid [6]. Infections have been reported to have a high diagnostic yield of 80% to 90% on aspiration [7]. Diagnostic yield has been attributed to larger lesion size and larger specimen length [8].

Fig 10

Cementoplasty
This involves injecting bone cement in the weakened weight-bearing bones to relieve pain. The procedure is usually named after the bone, which is treated. For example, acetabuloplasty when acetabular cementoplasty is done and sacroplasty (Fig 5A, B and C) when sacrum is treated.

Fig 11

Vertebroplasty and Khyphoplasty
Vertebroplasty and khyphoplasty, also know of vertebral augmentation techniques, involve injection of bone cement in the vertebral body to relieve pain and restore the height of the vertebral body [9]. Indications: Main indication of this procedure is to treat painful vertebral compression fractures which have failed conventional medical therapy. Most common cause is fracture due to primary osteoporotic disease. Others causes like steroid-induced osteoporosis (Fig 6A- C), metastatic disease, compression due to myeloma, hemangioma (Fig A-F) etc are also an indiction for these procedures [10].

Fig 12
Contraindications: Absolute contraindications are uncorrectable coagulopathy, spinal infection, vertebral infection and allergy to bone cement.
Special Considerations: Few of the following situations when present, should alert the interventional radiologist to take extra care during the procedure [11]-
1. Disruption of posterior cortex- increased risk of cement leaking into the spinal cord
2. Vertebra plana or marked loss in the height of the vertebral body
3. Epidural extrusion of tumor
4. Narrow central canal
Pre-procedure assessment and Imaging-
Pre-procedure history and clinical assessment is very important. Pain score before the procedure should be recorded.
Point tenderness at the spinous process should be elicited and correlated with the collapsed vertebra on imaging. A conventional spinal radiograph would be sufficient for this preliminary assessment. A lower limb neurological exam should also be performed. Routine laboratory investigations like complete blood count and coagulation profile should be done.
MRI is the test of choice for pre-procedure evaluation. It shows the exact site of marrow edema, the size of the spinal canal, the course of the exiting nerve roots and allows evaluation of epidural extension of tumor. At the same time, it will also help to make a definitive diagnosis on the etiology of the lesion. CT proves useful to evaluate the integrity of the posterior vertebral cortex.
Technique: Procedure is generally done in prone or oblique position. This position will facilitate extension of the fractured segments [12]. Local anesthesia with or without sedation is required. General anesthesia should be avoided as a conscious patient can alert the clinician about any new symptoms during the procedure.

Table 1
Routine pre-procedure antibiotic coverage in form of 1gm Cefazolin is given.
Approach: Generally, an 11 G needle is preferred for lower dorsal and lumbar vertebrae while a 13 G needle may be used for upper dorsal vertebrae. It is important to remember the orientation of the vertebral pedicles as one goes down the spine. Generally, two approaches are used to enter the vertebral body- the transpedicular approach and the parapedicular approach. The transpedicular approach has an advantage of protecting the nerve roots and the paravertebral tissue due to the long intraosseous course. The first step is to align the affected vertebral body in such a way that the spinous process is in the midline, the vertebral edges overlap and the pedicle is in the centre of that half of the vertebral body. The entry point is marked on the skin at about 10O’Clock position with respect to the pedicle that will be traversed. Lignocaine is infiltrated at that site and a small skin nick given with an 11 No blade. Needle is inserted from the planned entry point. For transpedicular approach, it is most important to keep the needle, lateral to the medial margin and superior to the inferior margin of the pedicle. This takes care that the needle is in the confines of the pedicle. The needle position could be checked on AP and lateral view on fluoroscopy. Once the needle reaches the posterior margin of the vertebral body, it should be further advanced till the anterior third of the vertebral body in lateral view and till the midline on AP view. Unipedicular approach would suffice if the cement crosses to the opposite side. Otherwise, a bipedicular approach is required [13]. For parapedicular approach, the vertebral body is directly entered and thus the needle is kept lateral to the lateral margin of the pedicle.

Table 2
Cement Injection for Vertebroplasty:
The cement commonly used is Polymethyl Methacrylate (PMMA). It comes in powder form with a solvent. The powder and solvent are mixed and left for few minutes. The cement is instilled through the needle when it has toothpaste like consistency. It is important to closely monitor leakage of cement in the spinal canal or along the nerve roots. The endpoints for cement injection include passage of cement beyond the marrow space and cement reaching the posterior quarter of the vertebral body. Mathis and Wong have recommended cement filling to 50-70 percent of the residual volume of the vertebral body [14].
Kyphoplasty: Before injecting cement, khyphoplasty involves an additional step of increasing the size of the vertebral body. This is achieved with a khyphoplasty balloon. Later, a dedicated Vertebroplasty injector system can be used to inject PMMA for khyphoplasty. It is recommended to treat up to 3 vertebral levels at a sitting to prevent the complications arising due to marrow fat embolizations [15].
When fractures with Intraosseous vacuum phenomenon (Kummell disease) is noted, it is important to place the needle as close as possible to the cleft in order to allow the cement to fill the cleft.
Complications: Common complications are pain, hematoma, cement extravasation along the nerve roots. Small amount of extraosseous passage of cement is seen in two-thirds of vertebroplasty. As against this, khyphoplasty has a lower rate since the cavity fills first with subsequent hardening of the cement. Other possible complications are paraspinal abscess, hypotension due to cement and fat emboli, pneumothorax, spinal cord damage due to cement extravasation and worsened pain [16]. The risk of complication is more while treating malignancy-related fractures.
Post-procedure monitoring and Follow-up:
The patient should lie supine for an hour after the procedure. Ideally, patient’s can be discharged later on the same day. NSAID’s can be prescribed for the procedure related pain. Many patients have significant relief of symptoms immediately after the procedure. Patient should be informed to report any sudden onset backache as this may indicate a new fracture. 3-week follow-up post-procedure is generally advised. At every follow-up, clinical and pain score assessment is important.
Radiofrequency Ablation: It involves ablating tissues by sending radiofrequency waves in the patient. Basic mode of killing cells involves generation of thermal energy around the electrode.
Principles [17,18]: The radiofrequency wave consists of an alternating current at high frequency (200 –1,200 kHz).
A closed loop circuit consisting of the RF generator, electrode, patient and ground pads (acting as a large dispersing electrode) in series is required. The electrode and the ground pads are active. The RF generator generates the RF current, which enters the tissue to be ablated through the electrode. This current leads to rapid oscillation of the molecules. The patient acts as a resistor. The friction generates heat, which kills the cells. The marked discrepancy between the surface area of the needle electrode and the dispersive electrode causes the generated heat to be tightly focused and concentrated around the needle electrode. The response of the tissue to heat depends on the temperature and the time for which heat was applied (Table 1).
Types of Electrodes: Major categories include monopolar devices, bipolar devices, and coblation devices.
1. Monopolar systems are most commonly used. These require a grounding pad placed on the patient. Their main disadvantage is the formation of aberrant currents, which do not always allow for uniform energy deposition inside the lesion.
They can be divided into single electrode and multi-tined. Single electrodes have the advantage of small caliber but have smaller ablation radius. They can feature hot, cooled-tip, and water-perfused. Multi- tined electrodes increase energy deposition by creating larger zones of ablation and produce better lesion destruction.
2. Bipolar devices do not require a grounding pad, because the current passes through the same or neighboring needles. Advantage is lesser aberrant currents.
Application of Radiofrequency Ablation in Orthopaedic Oncology:
A host of benign and malignant lesions can be treated with radiofrequency ablation. This include- Benign tumors like Osteoid Osteoma, Chondroblastoma, Aneurysmal Bone Cysts and Vertebral hemangiomas
Malignant tumors like spinal metastasis, ablation of soft tissue sarcoma’s to achieve local control.
Other non-oncology applications like radiofrequency neurotomy to treat backache are also practiced.
General Contraindications:
Absolute contraindications to ablation include coagulopathy disorders, skin infection, immunosuppression, and absence of a safe path to the lesion without harming vital organs or structures.
Radiofrequency Ablation for Benign tumors: Among the benign tumors, osteoid osteoma is the commonest benign bone lesion treated with RFA.
RFA of Osteoid Osteoma [18] (Fig 8A and B): It is a benign lesion, commoner in males (male: female = 4:1). It usually presents in the second decade with nocturnal pain, which is relieved by aspirin or other NSAID’s.
Imaging features: CT is the modality of choice. Typical lesion is seen in the cortex of a long bone with a centrally placed radiolucent nidus and a surrounding sclerotic rim. On contrast enhanced CT study, the nidus shows enhancement.
General technique: Percutaneous radiofrequency ablation is a reliable and effective technique that provides fast, long-lasting pain relief. Bourgault C et al recently published a paper treating 87 patients with osteoid osteoma. In this study, with mean follow-up of 34 months, the success rate for first-line treatment was 89.6% and it was 97.5% for second-line treatment. The recurrence rate was 10.4%.
RFA is generally done under CT guidance. Typically, the skin entry is achieved with a bone biopsy needle, which is advanced till the cortex. In cases where there is significant sclerosis, this thick bone is drilled using a bone drill. Once the lesion enters the lesion nidus, biopsy of the lesion is taken. Further, the RF electrode is inserted through the bore of the biopsy lesion into the lesion nidus. Before, ablation is commenced; the biopsy needle is withdrawn to prevent inadvertent heating of the surrounding tissues due to heat propagation via the needle. Otherwise, the biopsy needle can be exchanged for a hard introducer with a distal insulated tip over a K-wire. The presence of intact cortex around the lesion produces oven effect which leads to better ablation of the lesion.
RFA of other benign tumors: Condroblastoma, an epiphyseal tumor has been treated with RFA as an alternative to surgery. Rybak et al describes 17 patients with chondroblastoma for whom RFA was used as the primary treatment modality. On median follow-up of 41.3 months, 12 out of 17 patients showed complete relief of pain [19].
Aneurysmal bone cyst (ABC) has been treated by RFA of the epithelial lining followed by cementoplasty analogous to curettage and bone grafting. There have been reports where ablation of the ABC wall has been achieved using radioactive material [20].
There are some published reports on the treatment of other benign bone conditions such as enchondroma, eosinophilic granuloma, bone haemangioma and giant cell tumors.
RFA of Malignant tumors: This is usually done for pain relief with a palliative intent. In case of large tumors, compressing nerves, RFA can be performed to debulk the tumors. As RFA destroys cells and theoretically forms a cavity, cementoplasty can be performed along with the RFA to provide tensile strength [21, 22].

Embolotherapy for Musculoskeletal tumors
Transarterial embolization has been practiced for many years in both benign and malignant musculoskeletal tumors. The main purpose of these procedures is to reduce blood supply of the tumor, avoiding non-target embolization [23]. Embolization can be pre-operative embolization, serial embolization or palliative embolization. Pre-operative embolization aims to occlude as a much as possible, helping the surgeon to have a relatively bloodless field. Serial embolization aims to decrease to size of the tumor. This can relieve the patients of the symptoms like pain and in some, can make the patient fir for surgery. Palliative, as the name suggests aims to relive the patients of the symptoms and to improve the quality of life.
Technique: Generally, a pre-procedure cross-sectional imaging is helpful to see the extent and overall vascularity of the neoplasm. A pre-procedure assessment of platelet count, International Normalized Ratio (INR) and creatinine levels is necessary. Initially, a diagnostic angiogram is done to define the supplying vessels following which embolization is performed.
Gelfoam is the embolization material of choice for pre-operative embolization. In cases where serial embolization is required, particulate agents like polyvinyl alcohol (PVA) or embospheres is used. Coils are used where parent vessel occlusion is required or when protection of distal vasculature is necessary.
Embolotherapy in Benign Musculoskeletal Tumors: Embolization is generally performed for benign tumors like Giant Cell Tumor, Aneurysmal Bone Cyst, Vertebral Hemangiomas, Osteoblastomas and arteriovenous malformations.
Giant Cell Tumors (GCT’s)(Fig 9 A – D):
GCT’s radiographically appear as expansile lytic lesions in the metaphyseal region reaching the endplate. These have significant vascularity and are associated with significant blood loss.
Sacral GCT’s are especially associated with significant peri-procedure blood loss and post-surgical morbidity. In small operable GCT’s , embolotherapy aims to pre-operatively devascularize the tumor while in cases large sacral GCT’s, it aims to reduce the bulk of the lesion. It can also decrease the associated pain due to compression of the nerve roots [24].
Post-procedure increase in ossification of the lesion is a sign of favourable response to embolization.
In a series of 18 patients of GCT’s, managed with embolization, follow of 26 years showed durable response in 50% of patients with local recurrence rates of 31% in 10 years and 43% in 15-20 years [25].
Aneurysmal Bone Cyst (ABC) (Figure 10A and B): Though, curettage and resection are the primary treatment modalities of choice, embolization has been performed in recurrent ABC’s and as a pre-operative measure to reduce blood loss [26].
Vertebral Hemangiomas: Surgery is the modality of choice to treat vertebral hemangiomas causing cord compression or any neurogenic deficit. In these cases, pre-operative embolization serves as an adjuvant to surgery by reducing blood loss[27].
Arteriovenous Malformation of Bone:
Tranarterial embolization can prove as a useful treatment for AVM’s of bone. Direct puncture of the hemangioma with percutaneous embolization has also been attempted to control hemorrhage [28].
Other benign tumors like cervical spine osteoblastomas have been treated by embolization as a adjuvant to surgery.

Embolotherapy in Malignant Musculoskeletal Tumors
Metastases: Hypervascular metastases especially from thyroid and renal carcinomas are treated with embolization. The main intent is palliative and aims to reduce pain and other symptoms that may arise due to compression of the surrounding structures [7]. In 16 cases of renal cell carcinoma metastases bleeding was significantly reduced post embolization [29].
Metastatic spinal tumors (Fig 11A, B and C): Hypervascular spinal and pelvic tumors are treated with embolization as a pre-operative measure to decrease blood loss or as a palliative procedure to relieve symptoms.

Sclerotherapy of Bone Lesions
This involves instilling a scleroscent inside a bone tumor (especially a cystic bone tumor) to damage the lining endothelium, which eventually results in thrombosis.
Sclerotherapy using polidocanol has been attempted in treating Aneurysmal bone cysts (ABC) with encouraging results. In a paper written by Rastogi et al, the author has treated 72 cases of ABC’s with sclerotherapy with satisfactory result in more than 97% [70] of patients [31]. Significant reduction in size of the lesions has been documented. In hypervascular ABC’s, sclerotherapy can be preceded by embolization.

Percutaneous treatment of Vascular Malformation
Though congenital vascular anomalies are not bone lesions, these commonly present as a swelling and are referred to an orthopedic surgeon.
International Society for the Study of Vascular Anomalies (ISSVA) classifies congenital vascular anomalies into vascular tumors and vascular malformations.
Vascular tumors are hemangiomas, which are seen in infancy and childhood. They are further classified into infantile hemangioma, congenital hemangiona, Kaposiform hemangioendothelioma and tufted angiomas. Congenital hemangiomas are classified as Rapidly Involuting Congenital hemangiomas (RICH) and Non- Involuting Congenital hemangiomas (NICH) [32].
Vascular malformations can present anytime in life. They are classified as low-flow vascular malformations and high-flow vascular malformations.
Low-flow vascular malformations are namely venous malformations, lymphatic malformations or mixed while high flow vascular malformations are arterio-venous malformations and arterio-venous fistulas.
Diagnosis: These conditions are diagnosed on the age of presentation, the changes in the lesion over time (progression or regression) and some key imaging features.
Dyanamic Contrast MR Angiography (DCE_MRA) is the investigation of choice (33). Table 2 provides a review on the imaging features of few of the common vascular anomalies-

Treatment of Vascular tumors
Vascular tumors generally involute over time and eventually regress on follow-up. In cases of high flow lesions, endovascular angioembolization can be attempted to relieve symptoms or to decrease the vascularity before surgery.
Treatment of Vascular Malformations:
Low-flow vascular malformations are most commonly treated by percutaneous sclerotherapy.

Percutaneous Sclerotherapy (Fig 12A, B, C, D, E and F)
This involves injecting a scleroscent in the malformation, which leads to necrosis of the endothelium and subsequent thrombosis.
Contraindications: Atrial septal defects and pulmonary hypertension are absolute contraindications [34].

Technique for venous malformation
The procedure is performed under high quality digital subtraction angiography imaging with road-mapping technique.
The method of sclerotherapy depends on the angioarchitecture of the lesion. Vascular malformations are classified into sequestrated, non-sequestrated and mixed varieties. Sequestrated lesions do not have any communication with the deep venous system, making injecting scleroscent in the lesion safe. The non-sequestrated lesions have communication with the deep venous system while mixed lesions have both the features [35].
Procedure is generally performed under local anaesthesia. General anaesthesia with endotracheal intubation is required for lesions involving the oro-naso-laryngeal pathway or when severe pain is expected during scleroscent injection. Torniquent may be tied to decrease the venous outflow for malformations involving the extremities. Good hydration is necessary to counter scleroscent induced hemolysis.
Procedure: The lesion is punctured using 22G scalp vein needle or 22G spinal needle. Contrast injection is done to evaluate the angioarchitecture. In non-sequestrated lesions, scleroscent is injected into the lesion. For non-sequestrated lesions, outflow tract is occluded with a balloon catheter or glue or ablated with Nd-YAG Laser [36,37].
The commonest used scleorscent is sodium tetradecyl sulphate (Setrol). It is injected as foam. For radioopacity, it is mixed with oil-based solution like Lipiodol or non-ionic contrast. Not more than 0.5ml/kg should be injected at a time with a maximum permissible dose of 20ml [38].
Other scleroscents used are sodium morrhuate, bleomycin, doxyclycine, OKT-432 and ethanol.

Treatment for lymphatic malformation
These are classified as cystic or channel type. Cystic type is further classified as macrocystic, microcystic or mixed. These lesions present as large collections of lymph, commonly in the neck and the axillary lesions.
Lymphatic malformation is punctured with a needle under ultrasound (USG) guidance and fluid is aspirated with or without a pigtail catheter. Later, the scleroscent is instilled in the lesion. Doxycycline is the scleroscent of choice as it can be injected in large quantities [39].
Post-procedure monitoring:
Tight dressing and painkillers are given post-procedure. The lesion tends to increase in size for a few days due to imflammation. This generally settles with painkillers.
Complications: Pain, infection, hematoma and skin blistering are the general complications. Neuropathy may be seen after ethanol injection. Compartment syndrome is a dreadful complication seen when sclerotherapy is done in closed spaces like the orbit. Hemolysis and hemoglobinuria is seen when large amount of scleroscent is used. Other rare complications are pulmonary edema and acute cardiovascular collapse [40].

Advances in Interventional Orthopediac Oncology
Isolated Limb Infusion (ILI) for Malignant Extremity Bone Tumors:
This is a comparatively new approach of delivering high dose of a chemotherapeutic agent in the limb in which the tumor is present. The main advantage is larger quantity of dose of the chemotherapeutic agent can be administered with less systemic side-effects.
ILB has been attempted for melanoma using Actinomycin-D and for soft tissue sarcoma’s using melphalan and tumor necrosis factor [41].
MR-HIFU (MRI-guided High Intensity Focused Ultrasound) [42]:
This involves focusing high intensity ultrasound beam in the desired tissue to be treated. The ultrasound waves cause heat generation in the tissue with coagulative necrosis. MRI is used to guide the treatment. In orthopedic oncology, MR-HIFU can be used for ablation of painful bone metastasis and local tumor control in infiltrative tumors.
Cryoablation [43]: Like radiofrequecy ablation destroys tissue by heat, cryoablation damages tissue by extreme cooling to sub-zero temperatures. It is indicated for painful bone metastasis and for local tumor control. Use of thermocouples to measure temperature is sometimes indicated to prevent damage to surrounding nerves is some cases.

Conclusion

Interventional Radiology has an ever increasing role in the diagnosis and management of bone and soft tissues tumors. Close co-operation and discussions with the orthopedic oncologist and interventional radiologist is the cornerstone for selection of correct treatment modality and optimizing response.

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22. Fernando Ruiz Santiago, María del Mar Castellano García et al Treatment of bone tumours by radiofrequency thermal ablation Curr Rev Musculoskelet Med. Mar 2009; 2(1): 43–50.
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How to Cite this article: Pendse H, Kulkarni A, Agarwal M. Role of Image Guided Interventions in Orthopaedic Oncology. Journal of  Bone and Soft Tissue Tumors Sep-Dec 2015;1(2):  25-33.
h A 

Dr. Aniruddha Kulkarni

 m 

Dr. Manish Agarwal

(Abstract)      (Full Text HTML)      (Download PDF)

 

 

High dose Methotrexate in Paediatric Osteosarcoma – a brief overview

Vol 1 | Issue 2 | Sep – Dec 2015 | page:22-24 | Reghu K S[1], Vivek S Radhakrishnan[1]

Author: Reghu K S[1], Vivek S Radhakrishnan[1]

[1]Aster Medicity Cheranallur Cochin, India.

Address of Correspondence
Dr. Reghu KS
Aster Medicity Cheranallur Cochin, India.
Email: reghuks@gmail.com

Abstract

Systemic combination chemotherapy protocols have significantly impacted the survival rates in paediatric osteosarcoma. A number of drugs have been found effective and high dose methotrexate (HDMtx) is of them. The clinical data available on use of HDMtx is still not clear about the effectiveness and metanalysis have found that evidence is still inadequate to recommend routine use. Few studies have strongly reported improved survival rates with high dose methotrexate and this led to more trials using the drug in standard treatment arm. However there are other studies that have failed to show any survival advantage. In this review we discuss the biology of osteosarcoma with relevance to Methotrexate, clinical trials evaluating the use of High dose Mtx in treatment of OS and recommendations based on available evidence.
Keywords: Methotrexate, Osteosarcoma, Evidence.

Introduction

The introduction of systemic combination chemotherapy has dramatically improved the survival of pediatric osteosarcoma (OS). Various combinations of chemotherapeutic agents have been tried by different study groups and centres and the common agents that have emerged as effective are Adriamycin, cisplatin, Ifosfamide, Etoposide and High does Methotrexate. The overall survival using various combinations of these agents have more or less been similar. The role of methotrexate in treatment of pediatric OS has been a contentious issue even after decades of its use. Methotrexate (Mtx) was introduced in the 1960s by for treatment of osteosarcoma by Norman Jaffe and has been a standard component of chemotherapy for pediatric OS. However evidence for high dose Mtx having an independent impact on survival is controversial. In this review we discuss the biology of ostesarcoma with relevance to Mtx, clinical trials evaluating the use of High dose Mtx in treatment of OS and recommendations based on available evidence.

Biological rationale for the use of High dose Methotrexate (HDMtx)
Methotrexate is a structural analog of folic acid that binds to dihydrofolate reductase (DHFR), and inhibits the folate metabolism in tumor cells. Polyglutamylated form of Mtx is retained in the cells better and it effectively blocks DHFR. Methotrexate is transported into the cell by the folate receptors, the reduced folate carrier (RFC), and the proton coupled folate transporter, out of which the RFC is the most relevant. Osteosarcoma tumor cells show one or more sequence alteration in the RFC gene or decreased RFC mRNA expression. Increased DHFR mRNA expression is also common ,especially in metastatic disease. These mechanisms cause OS tumor cells to be inherently resistant to standard doses of Mtx [1]. However this resistance can be overcome with higher than standard dose of Mtx which may allow transport through alternative means, such as passive diffusion and by prolonged drug exposure. Doses of 8gm/sq.m to 12gm/sq.m of Mtx are usually used in most protocols.

Evidence from Clinical trials
The data from clinical trials regarding the effect of HDMtx on survival have been ambiguous. HDMtx was incorporated as a standard component of therapy without the rigorous evidence from randomized control trials, mostly based on experience from single centre cohorts. Bacci et al demonstrated that patients receiving HDMtx had higher overall survival rates at 5 years. For patients receiving HDMTX therapy a rate of 58% was reached versus 42% for patients treated with intermediate dose MTX. MTX levels after HDMtx administration had a significant effect on survival [2]. Complete remission rate at surgery was related to serum levels and at levels below 700 micromole/liter complete remission rates were 9.9% while it was 28% at higher levels. Another randomized trial compared doxorubicin/ Cisplatin versus HDMtx with reduced dose doxorubicin and cisplatin. Disease-free survival was inferior in patients who received the 3 drug arm but overall survival was not significantly different between both treatment arms. However, the intensity of administration of MTX was compromised by the design of the study [3]. Non-methotrexate containing chemotherapy was found to be a poor prognostic factor in some studies [4]. There also have been studies which failed to show any survival benefit with HDMtx containing regimes. A randomized study conducted by the Children’s Cancer Study Group comparing HDMTX and intermediate dose Mtx in combination with doxorubicin and vincristine as adjuvant therapy did not show any benefit of HD- Mtx [5]. The results from St.Judes OS99 trial in which all patients were treated with a 3 drug non-methotrexate regimen consisting of carboplatin ,doxorubicin and Ifosfamide had favorable outcomes compared to HDMTx regime used previously by the same group [6]. The European Osteosarcoma Intergroup (EOI) compared a 2-drug regimen (doxorubicin, cisplatin) with a multi-drug regimen (HDMtx, doxorubicin, bleomycin, cyclophosphamide, dactinomycin, vincristine, cisplatin) and no difference in survival between the 2 arms was seen [7]. The frequency of MTX dosing was decreased to allow the administration of doxorubicin when compared with the multi-drug scheme similar to the T-10 Rosen scheme and with the presence of other active drugs the contribution of HDMtx was difficult to demonstrate. Attempts to enhance the efficacy of MTX-L in osteosarcoma by extending the period of administration from 4 or 6 hours to 24 hours or prolonging the interval before initiating the rescue program have not been successful. Administering a high Mtx dose by the intra-arterial route, which produces a higher local concentration, also did not enhance the efficacy.

Considerations for the Clinic Administration of High dose Methotrexate
HDMtx administration when done in centres with adequate expertise has a good safety profile. Diligent monitoring of hydration, urine pH, renal function and serum methotrexate level monitoring are absolutely needed for HDMTx administration. Protocols have to be written down, staff should be well trained and supervised in such centres. Leucovorin rescue by administering folinic acid intravenously based on serum methotrexate level monitoring is the key to successful HDMtx therapy. Algorithms to calculate leucovorin dose based on serum methotrexate levels and time interval following Mtx administration must be used. Hydration also has to be continued till the serum Mtx levels have decreased to less than 0.1 micromol/L to 0.3 micromol/L. Drugs like penicillins , NSAIDs which interfere with Mtx excretion must not be used concomitantly. Use of carboxypeptidase should be considered if serum methotrexate concentration is >10 micromol/L more than 48 hours after methotrexate administration or if there is a rise in creatinine of 100% or more within 24 hours of methotrexate. It reduces mtx levels dramatically within minutes of administration. Access to Glucarpidase when required is recommended.
HDMtx must be avoided in case of pleural effusion or ascites due to retention and slow release of Mtx .
Complications that can occur with HDMtx are renal failure, severe mucositis, myelosuppression and encephalopathy.

Mechanisms of Methotrexate Resistance in Osteosarcoma
DHFR gene amplification and impaired transport of Mtx are two common mechanisms of acquired resistance observed. Decreased RFC expression was associated with a worse histological response to preoperative chemotherapy that includes HDMtx treatment. Increased DHFR expression represents acquired MTX resistance and is an uncommon mechanism for intrinsic resistance [8]. Emergence of a resistant clone or acquisition of DHFR gene mutations could be the underlying causes. Rb gene mutations which are common in OS cause elevated E2F expression and is proposed to elevate the DHFR levels [9].

Challenges in developing nations
The scenario in developing nations like India has been gradually improving. But the survival rates are still low compared to the developed nations. There is a lack of data regarding treatment details and survival outcomes in pediatric OS. Most centres in India use Cisplatin/doxorubicin based regimes which do not contain HDMtx. In a yet to be published study from a high volume cancer centre in India, survival figures of pediatric OS treated with cisplatin/Adriamycin/Ifosfamide chemotherapy the overall OS and DFS were 54.6 and 43.4 respectively at 3 years (personal communication). The DFS was 0% at 3 years for patients with metastatic disease at presentation. Similar experience is shared by other centres in the country using non-methotrexate regimes.
Though it is tempting to consider addition of HDMtx in such a scenario , the limited resources in developing nations precludes its routine use for pediatric OS. Lack of facilities for Mtx level monitoring, high infection rates , underlying malnutrition, inadequate supportive care facilities makes it difficult to administer HDMtx to most of the pediatric OS patients in India.

Current recommendation
Based on available studies a Cochrane meta-analysis concluded that data is inadequate to make a definite recommendation for HDMtx [10]. It seems unlikely that there will be in the future any large RCTs to unequivocally establish the superiority of HDMtx. Despite this, HDMtx is an essential component of standard arms of ongoing trials. The recent EURAMOS trial has 12gm/sq.m of Mtx in the neoadjuvant chemotherapy phase for all patients [11]. Absence of RCTs should not dissuade the addition of HDMtx, especially in centres which have poor outcomes with non-methotrexate chemotherapy regimes. Addition of HDMtx may provide an edge over existing chemotherapy and should be attempted , provided that the prerequisites for HDMtx therapy as discussed above are available. One approach could be to try HDMtx for high risk OS patients first and based on the experience gathered, treatment may be extended to standard risk patients as well.

References

1.Posthuma De Boer J, van Royen BJ and Helder MN. Mechanisms of therapy resistance in osteosarcoma: a review. Oncol Discov. 2013; 1:8
2.Bacci G, Longhi A, Versari M, Mercuri M, Briccoli A, Picci P. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer. 2006 Mar 1;106(5):1154–61.
3.Gelderblom H.Survival after recurrent osteosarcoma: data from 3 European Osteosarcoma Intergroup (EOI) randomized controlled trials.Eur J Cancer. 2011 Apr;47(6):895-902.
4.Luetke A, Meyers PA, Lewis I, Juergens H. Osteosarcoma treatment – where do we stand? A state of the art review. Cancer Treat Rev. 2014 May;40(4):523–32.
5.Krailo M.A randomized study comparing high-dose methotrexate with moderate-dose methotrexate as components of adjuvant chemotherapy in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group. Med Pediatr Oncol. 1987;15(2):69-77.
6.Daw NC, Neel MD, Rao BN, et al. Frontline treatment of localized osteosarcoma without methotrexate: results of the St. Jude Children’s Research Hospital OS99 trial. Cancer. 2011;117:2770–8.
7.Craft AW .Osteosarcoma: the European Osteosarcoma Intergroup (EOI) perspective.Cancer Treat Res. 2009;152:263-74.
8.Wang J, Li GJ .Relationship between RFC gene expression and intracellular drug concentration in methotrexate-resistant osteosarcoma cells Genet Mol Res. 2014 Jul 24;13(3):5313-21.
9.Sowers R.mRNA expression levels of E2F transcription factors correlate with dihydrofolate reductase, reduced folate carrier, and thymidylate synthase mRNA expression in osteosarcoma.Mol Cancer Ther. 2003 Jun;2(6):535-41.
10. van Dalen EC, van As JW, de Camargo B. Methotrexate for high-grade osteosarcoma in children and young adults. Cochrane Database of Systematic Reviews 2011, Issue 5. Art. No.: CD006325
11.Whelan JS, Bielack SS, Marina N, et al. EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment. Annals of Oncology. 2015;26(2):407-414.
12. Xu M,Xu SF,Yu XC.Clinical analysis of Osteosarcoma patients treated with high-dose methotrexate-free neoadjuvant chemotherapy. Current Oncology. 2014;21(5):e678-e684

How to Cite this article: Reghu KS, Radhakrishnan VS. High dose Methotrexate in Paediatric Osteosarcoma – a brief overview. Journal of  Bone and Soft Tissue Tumors Sep-Dec 2015;1(2): 22-24 .
R  
              Dr. K S Reghu
 V

Dr. Vivek S Radhakrishnan

     

CAOS in Paediatric Bone Tumour Surgery

Vol 1 | Issue 2 | Sep – Dec 2015 | page:17-21 | James E. Archer[1], Philippa L. May [2], Lee M. Jeys[1,2*]

Author: James E. Archer[1], Philippa L. May[2], Lee M. Jeys[1,2*]

[1]The Royal Orthopaedic Hospital, Bristol Road South, Birmingham, B31 2AP, UK.
[2]College of Medical and Dental Sciences, University of Birmingham, Edgbaston, B15 2TT, UK
[3]Professor of Health and Life Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK

Address of Correspondence
Professor Lee M. Jeys, MBChB, MSc (Ortho. Engin.), FRCS (Tr. & Orth.), Professor of Health and Life Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK.
e-mail: lee.jeys@nhs.net

Abstract

Surgical navigation has been used by neurosurgery for a number of years as a method for accurately locating and resecting tumours within the brain. The anatomy of bony structures does not alter between image acquisition and the surgical procedure, therefore computer assisted technology lends itself well to use in orthopaedic surgery. Studies have demonstrated that this technology improves orthopaedic surgical accuracy across a wide breadth of procedures such as arthroplasty, knee ligament reconstructions and more recently, bone tumour surgery. This article aims to identify the importance of this new technology in paediatric bone tumour surgery and give an overview on its use.
Key Words: Computer assisted orthopaedic surgery, Paediatric, Oncology.

Introduction

Paediatric orthopaedic tumour surgery is one of the most challenging areas of orthopaedic oncology. Tumours can be found in a number of regions, with the pelvis being one of the most challenging. The removal of a tumour, post-operative complications and need for revision, all have a large impact on quality of life in paediatric patients. The complexity of the pelvic region and the associated nerve and organ structures mean that surgical excision of tumours must be very precise. Resection without Computer Asissted Orthopaedic Surgery (CAOS) has a high rate of local recurrence because of the difficulty of achieving a wide local excision [1]. The use of computer assisted technology in sarcoma surgery has improved surgical outcomes by reducing local recurrence, reducing revision rates and by decreasing the rate of amputations and nerve root damage [2,3].

The tumour types
Two tumour types are often seen in the pelvis in the paediatric population. Osteosarcomas are the most common primary bone tumour and they are most commonly seen in teenagers and young adults. They form approximately 20% of all primary bone tumours and approximately 8% of these will be found in the pelvis [4].

Table 1 2
Ewing’s sarcoma is a rarer tumour, with around 65-75 cases per year in the UK. It is far more common in the paediatric population with a median age at diagnosis of 15 [5]. Pelvic Ewing’s sarcoma is seen in 26% of all patients [6].
In the UK, pelvic Ewing’s sarcoma are often treated pre-operatively with chemotherapy plus either radiotherapy or proton therapy. This makes surgery in the pelvis even more challenging and also has led to an increasing trend not to perform reconstruction due to the high risk of complications. This therefore makes protecting nerve roots and the hip joint essential to maintaining function.

Table 3
While these tumours in the pelvis are rare and do not represent a large case load, they are often significantly advanced at the time of presentation. This is in part due to their rarity, but also due to the fact that localised symptoms only become apparent late in the condition as the pelvis can contain a large tumour without displaying symptoms. Also because of the young age of the patients, the impact on quality of life and functionality can be significant. This is especially true when considering the extent of surgical intervention that children often require. The length and complexity of surgery also means complications such as infection, dislocation and recurrence are high.
CAOS has been used less frequently in the lower limbs at our centre but has been used at other units extensively [7]. One case of the use of CAOS in the lower limb is presented in this article. Other applications for CAOS include its use in biopsy and for radio-frequency ablation [8].

Figure 1

The Challenge of Pelvic Surgery
There are a number of features which make pelvic oncological surgery challenging and it therefore requires experienced and highly skilled surgical intervention.
The first feature of note is the average size of tumours, at presentation primary pelvic tumours tend to be extremely large as the symptoms of a tumour in this region are often attributed to other causes such as musculoskeletal pain. Furthermore, swelling can be non-palpable due to its location and the overlying muscle. These features in combination tend to mean that pelvis tumours are large at presentation, on average 628cm3 [9].
The underlying anatomy of the pelvis itself also makes this a challenging area to perform surgery. The pelvis is a large, complex three-dimensional structure with numerous nerves and friable soft tissues present. Because of its size and complexity, patients often have to be moved intra-operatively to facilitate appropriate access to the pelvis.

Fire 2
The tumours themselves also contribute to the difficulty of surgery. They frequently contain cystic lesions which may burst, furthermore they also can be weaker than the surrounding healthy bone structure leading to fracturing of the tissue to be removed.
Furthermore, achieving a wide local excision of the tumour can be challenging. As discussed, these tumours tend to be discovered late, therefore they can have invaded into local soft tissue structures. Attempting to maintain joint, hip capsule and articular surfaces can help to maintain function but may impact on the completion of a wide local excision. These difficulties in resection of the tumour have led to the high rate of local recurrence reported [10], due to inadequate resection margins, both intra-lesional and marginal.
One study looked at the success of wide local excision margins in the pelvis, in experienced surgeons, operating on model pelvises in ideal conditions. The probability of them obtaining a suitable margin was 52%, highlighting the difficulty of obtaining appropriate margins for surgical resection [11].
The primary aim of the surgery is of course excision of the tumour but an important secondary outcome is to ensure function. Reconstruction using a one-size fits all prosthesis is not possible in the pelvis due to the complexity of the mechanics of the pelvis. Therefore, individual prosthesis are required, which fit effectively to prevent further revision being required. In those fitted with an endoprosthesis the 5 year survival of the prosthesis was 76% [10], compared with 87% survival at 12 years for those who undergo massive allograft reconstruction [12].
Once all of these other features have been overcome, the rates of complication are also high, due to all of the factors identified above. Three major case series have reported their complications and the data is included in the table below. They have reported complication rates of greater than 50%, with infection, local recurrence and dislocation being the major contributors as shown below (Table 1).
How can we improve these outcomes?
There are a number of features that have been targeted to try and improve outcomes.
Firstly, blood loss during surgery can be significant, as shown in the studies below. Every study shows an average blood loss of greater than 2.5 litres, which in a paediatric population represents a significant volume of blood loss (Table 2).
One method for reducing blood loss is hypotensive anaesthesia. By maintaining patients at a lower mean arterial pressure, the amount of bleeding can be reduced. A retrospective study using hypotensive epidural anaesthesia compared to standard anaesthetic technique was performed at The Royal Orthopaedic Hospital, Birmingham [20]. This showed that blood loss was significantly reduced by using this technique (Table 3).
The other big advance has been the use of CAOS. CAOS works effectively in the pelvis for a number of reasons. Firstly, the bony structure of the pelvis allows for multiple bony landmarks to be used as reference points. The registration of landmarks allows the computer to orientate itself correctly within space and therefore build up a correlation between the saved images and the three dimensional structures that are present. This correlation is what allows such accuracy at the time of surgery and helps to ensure an adequate wide local excision by accurately delivering the pre-operative planned resection to within 1mm.
The image required for CAOS is also important as both CT and MRI offer benefits. CT images provide good detail of the bony structures, but MRI provides more information on the soft tissue structures and the extent of the tumours. Therefore, fusion of these imaging modalities has been performed [21] which allows for a more complete pre-operative planning image. As technology advances further imaging modalities have been fused into this process including PET scans and angiograms.
There have been some reports of improved intraoperative registration being achieved by implanting four Kirschner wires, two in the iliac crests and two in the posterosuperior iliac spines, to act as permanent markers. The implantation of these wires helps to offset any error that may be produced by orientation difficulties and further enhances the accuracy of surgery within a delicate region [22].
Use of CAOS has shown a reduction in local recurrence rates from 26% to 13% at a mean follow up of 13.1 months [2]. While this has not completely removed local recurrence, it is a significant reduction in preliminary practice. The authors suggest that as surgeons become more practiced in using the CAOS technology, further improvements could be seen. The importance of minimising registration errors is highlighted, as this can help to ensure good accuracy of the surgery and therefore good surgical margins can be achieved. One element of this registration accuracy is to ensure that the time between image acquisition and surgery is minimised.
Finally, the design of custom made implants has also been made possible by the precise planning and good quality pre-operative images. Using the planning images, and the exact measurements and angles allowed by this process, the engineer can effectively design a custom implant which will fit exactly. This has previously not been possible as the surgeon would need to make a judgement at the time of the procedure regarding the extent of resection, so a pre-planned prosthesis, custom made to fit exactly to the patient was not always feasible. Good communication between the engineer and the planning surgeon is essential to ensuring that the implants will work effectively.

Case Illustrations
To highlight the importance of CAOS we now briefly discuss two cases which were performed at The Royal Orthopaedic Hospital, Birmingham using CAOS.
The first case is a case of a pelvic Ewing’s sarcoma. The presentation MRI is shown below (Fig. 1). The case was discussed at the National Ewing’s sarcoma MDT meeting, the location of the tumour made surgical resection very challenging as there was significant risk of damage to the L5, S1 and S2 nerve roots. She was initially given four cycles of chemotherapy and then re-discussed at the MDT meeting. Despite the high risk, the decision was made to combine surgery with radiotherapy as it was felt this would probably give the best outcome. The significant morbidity risks were discussed with the patient and her family. They decided to proceed with surgery. She underwent a computer assisted hemisacrectomy after pre-operative chemotherapy and radiotherapy with a good response. The images below show images from the planning software and then the orientation of the navigation technology (Fig. 1c,d,e). The operation was successful and managed to preserve the nerve roots and histology confirmed complete necrosis of the tumour. The images below show her post-operative recovery (Fig. 1b,f). No further radiotherapy was therefore required. She made a good post-operative recovery and progressed so well that she was able to Ski one year after the procedure, where she fell and fractured her pelvis. This has now healed and she can walk an unlimited distance and is wakeboarding!
The second case is a lower limb Ewing’s sarcoma. The presentation X-ray and MRI images are shown in (Fig. 2a,b). He underwent neo-adjuvant chemotherapy and had a good response to this. He then underwent a computer assisted radiation reimplantation of his right femur. His femur was removed and irradiated with 90 Gy of radiotherapy (Fig. 2 c,d,e). He made a good post-operative recovery and histology confirmed complete necrosis of his tumour. The post-operative images below show good fixation was achieved (Fig. 2 f,g). He completed his post-operative chemotherapy and made an excellent recovery with full weight bearing and good union of his osteotomies (Fig. 2h,i) show his follow-up x-ray and an image of him walking to demonstrate normal function.

Conclusion 

The use of CAOS has increasing evidence of providing improved outcomes. Early results seems to suggest decreased local recurrence, reduced rates of revision and decreased need for amputation (2). One of the major improvements offered by CAOS is the reduction in intra-lesional resection rates (1,23,24).The increased accuracy afforded by CAOS also allows for better fitting implants with better biomechanics, therefore helping to reduce complications and the rate of revision.
Surgical planning time is currently longer when CAOS is used, however it is felt that as surgeons become more practiced this time will reduce. Furthermore, the currently increased time taken is likely worth it for the improvement in outcomes. Currently unpublished data from this centre also shows that there is a reduced operative time when CAOS is used.
While cost-effectivity of this approach has not been assessed, the reduced complications and potential for reducing local recurrence would appear to point to a long-term cost saving by using this approach to paediatric bone tumour surgery in the pelvis.

References

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How to Cite this article: Archer JE, May PL, Jeys LM. CAOS in Paediatric Bone Tumour Surgery. Journal of  Bone and Soft Tissue Tumors Sep-Dec 2015;1(2):17-21.
J
              Dr. James E. Archer 
 P

Dr. Philippa L. May
L
                Prof. Lee M. Jeys   

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Limb Salvage in Paediatric Bone Tumours

Vol 1 | Issue 2 | Sep – Dec 2015 | page:10-16 | Michael Parry[1], Robert Grimer[1]

Author: Michael Parry[1], Robert Grimer[1]

[1] The Royal Orthopaedic Hospital, Birmingham, UK.

Address of Correspondence
Dr. Michael Parry.
Royal Orthopaedic Hospital NHS Foundation Trust
Bristol Road South ,Northfield, Birmingham
B31 2AP, United Kingdom
Email: michael.parry3@nhs.net

Abstract

Significant progress has been made in the management of paediatric osseous sarcoma. Where historically this diagnosis conferred a dismal prognosis, modern strategies of oncological management have resulted in significant improvements in disease free survival. These improvements have resulted in a broadening of the feasibility of limb salvage, which, in the paediatric population, presents its own unique challenges. Treatment must prioritize life over limb and not compromise local control for the advantage of cosmesis, limb length or function. Limb salvage, where possible, offers distinct advantages over conventional amputations and with the advent of modern techniques and technologies, should always be a consideration in the paediatric sarcoma population.
Keywords: Limb salvage, paediatric sarcoma.

Introduction

Primary malignant tumours arising from bone are relatively rare in the paediatric and adolescent population, accounting for only 6% of childhood malignancies. Of these, the majority (>90%) comprises osteosarcoma and Ewing’s sarcoma. Other bone sarcomas including chondrosarcoma, malignant fibrous histiocytoma, fibrosarcoma, malignant giant cell tumours, and adamantinoma can occur in the paediatric population although their incidence is relatively low. In these rare tumours, surgery is the first choice for local control.
Historically, an extremity sarcoma in a child conferred a dismal prognosis. However, advances in imaging modalities, greater understanding of the role of local control, and the use of multi-agent chemotherapy, has resulted in a significant improvement in overall survival. Such advances have resulted in an increase in 5-year survival from 10-20% to 60-70% with modern techniques. Thanks to these improvements in overall survival and a groundswell of interest and advances in technology, limb salvage is now regarded as the gold standard of treatment for those presenting with osseous extremity sarcoma. Advances in bone banking and an appreciation of the behavior of prosthetic replacement have improved surgical outcomes in limb salvage, though they have created their own complications. The aim of this review is to explore the advances in limb salvage surgery for osseous sarcoma in the paediatric population.

Patient Assessment and Diagnosis
Patients presenting with a suspected sarcoma should be managed in a specialist institution with the expertise and multi-disciplinary facilities necessary for the holistic care of the patient throughout their cancer journey. This is no more apparent than in the paediatric population where treatment decisions must be agreeable not only to the patient but also to their parent or carer.
In all patients, a detailed history and examination is mandatory. Whilst the majority of sarcomas are sporadic, rare familial conditions, including Retinoblastoma and Li Fraumeni syndrome, should be identified. The physical examination must include assessment not only of the lesion but also the distal neurovascular status of the limb.
Radiography must include a plain radiograph of the affected bone or limb segment as this will form the basis of the diagnosis. Further, detailed cross sectional imaging, most commonly with magnetic resonance imaging (MRI) will allow local staging. Systemic staging of the disease necessitates computerized tomography (CT) of the chest, as well as skeletal imaging, either in the form of a technicium Tc-99m scan, or whole body MRI. Systemic staging may include positron emission tomography (PET) in conjunction with a CT scan, though this is dependent on local and institutional guidelines.
Biopsy remains the cornerstone of confirmation of diagnosis for any suspected malignancy arising from bone. Improperly performed biopsies can result in a delay in treatment, hinder subsequent attempts at limb salvage, and result in an increase in local recurrence. MRI prior to biopsy helps identify the optimal position for biopsy and avoids distortion of the imaging by post-biopsy changes. The biopsy should be performed in such a way that the tract can be completely excised at the time of definitive resection and should be performed by a surgeon familiar with the techniques of limb salvage. The use of image guidance with ultrasound or CT is especially pertinent in the paediatric population where considerable contamination can occur with open biopsy techniques.

General Treatment Considerations
It is imperative that discussions regarding treatment are conducted in the setting of a multi-disciplinary team including specialists in paediatric oncology, radiology, histopathology and orthopaedic oncology surgery. Having established the diagnosis, in terms of histological type and grade, and staged the local and systemic burden of disease, discussion turns to local control. The timing of local control varies dependent on diagnosis and stage. Most strategies utilize systemic chemotherapy prior to definitive local control. This allows the treatment of metastatic or suspected micro-metastatic disease to be instigated immediately. This time lapse allows careful planning of the definitive surgical resection, allowing time for custom made implants or grafts. It also allows an assessment to be made of the tumour response to neo-adjuvant therapies, which often guides adjuvant therapy following tumour resection. In some cases, neo-adjuvant therapy results in a dramatic change in the tumour facilitating subsequent resection. The modality for local control must take into consideration patient, tumoural, socio-economic, cultural and technical biases.

Amputation versus Limb Salvage
Whilst no absolute contraindications to limb salvage exist, the involvement of neurovascular structures which preclude attainment of a clear margin without significant impairment of limb function, and very young skeletal age, should point away from limb salvage as the definitive local control. Relative contraindications include factors resulting in a delay in reinstating systemic therapy, including infection and post operative wound complications, and factors most likely to result in an increase in local recurrence, including tumour bed contamination from inappropriate biopsy, expected positive surgical margins and pathological fracture (Fig. 1).

Fig 1 2 3
Patient wishes must be respected when considering amputation or limb salvage. The majority of studies comparing function in these two treatment groups have looked at tumours of the distal femur. No statistically significant difference has been demonstrated in the overall or disease specific outcomes between these two approaches, which is a manifestation of appropriate patient selection. According to the available outcome scores, function following amputation is comparable to that of limb salvage, with comparable psychological end points. Patients with limb salvage will often have a superior cosmetic result but often at the expense of endurance in certain physical activities. Patients undergoing limb salvage will undergo more surgical interventions than their amputation counterparts and patients and their families should be made aware of the lifetime of surveillance and repeated surgical interventions at the outset. However, financial considerations should not sway the intervention, especially as amputation patients will require a greater lifetime expense than their limb salvage counterparts.

Limb Salvage Surgery
When considering surgery for local control in osseous malignancies of the immature skeleton, consideration must be given to the tumour location and the sensitivity to oncological treatment modalities. For tumours sensitive to chemotherapy and radiotherapy, (especially Ewings sarcoma), in challenging locations where surgical resection will result in unacceptable morbidity or an uncontaminated margin will be difficult to achieve, then non-surgical interventions may be more appropriate. Alternatively, for tumours not sensitive to radiotherapy, such as osteosarcoma, surgical resection may be the only option for local control, regardless of the morbidity. Surgery for the primary tumour and for metastatic deposits should be considered wherever possible. The aim in all surgery is to obtain as wide a margin of clear tissue as possible around the tumour. The better the response of the tumour to neoadjuvant treatment the safer limb salvage surgery becomes. Local control is indispensible for the cure of patients with Ewing’s sarcoma. Intralesional resection is associated with an increased risk of local recurrence and distant metastases.

FIg 4 5

Resection Without Reconstruction
For tumours arising in dispensable bones in the immature skeleton, including sections of the ulna, the scapula, the sacrum, the pelvis and fibula, local control can be achieved through excision without reconstruction. Excellent functional outcomes can be achieved without reconstruction, more so in the adaptable paediatric population.

Resection and Reconstruction
Biological Reconstruction
Autograft The large bony defect created following resection of an osseous malignancy often necessitates reconstruction for preservation of function and continued skeletal growth. The use of non-vascularised autologous structural bone graft dates back 100 years  , whilst the use of a vascularized fibula graft was first described by Taylor in 1975. The blood supply of the vascularized graft is preserved by anastomosing its feeding vessel to a host artery. The graft subsequently undergoes revascularization from this vessel and from the surrounding vascular bed. Since its first description, this technique, as well as the use of non vascularized grafts, has been extensively described and applied. The technique lends itself best to reconstruction of intercalary long bone defects, or for proximal humeral osteoarticular reconstruction where the fibula provides not only structural support but also allows longitudinal growth of the limb segment from the proximal physeal plate. Special consideration should be given to resection of pelvic sarcomas where autograft reconstruction is being considered. An option for reconstruction in the adolescent age group, at or approaching skeletal maturity, is resection, extracorporeal sterilization and reimplantation. This has been reported as a viable method for reconstruction. Indeed, in their latest series reporting the use of this technique, Wafa et al   reported a successful outcome in patients as young as 8 years old. This technique can also be applied to other body sites, particularly for intercalary reconstruction (Figs. 2 &3).
Allograft Improvements in tissue banking have allowed an expansion in the use of cadaveric osseous and osteoarticular allografts. Grafts are harvested and sterilized either by freezing or irradiation and can be offered on a custom made, size matched basis. There are mixed reports on the viability of articular cartilage following sterilization and the cadaveric bone itself is incorporated at best only moderately at osteosynthesis sites and beneath the periosteal sleeve, making the allograft at best a biomechanical scaffold. Depending on the site of reconstruction, up to 50% of patients undergoing allograft reconstruction can expect at least one complication, including infection, non-union or graft fracture. Some have reported infection rates following allograft reconstruction to be twice that seen following reconstruction with an endoprosthetic replacement. In spite of these potential problems, patients who avoid complications following allograft reconstruction function at a high level without the requirement for repeated revision procedures seen in endoprosthetic replacement.
In the case of adamantinoma and osteofibrous dysplasia like adamantinoma of the tibia, resection and reconstruction can be achieved either without reconstruction in the case of small, unicortical lesions, or with reconstruction using allograft, or autologous fibula graft. The fibula can be transferred and stabilized either in conjunction with a tibial allograft stabilized with plates or with the assistance of a ring external fixator.
In cases of diaphyseal resections, reconstruction can be achieved with intercalary allograft where the native joint above and below the lesion can be preserved. In many cases, particularly in Ewing’s and osteosarcoma, the tumour extends to the metaphysis, sparing the physis. Careful dissection can allow removal of the tumour without injury to the physis, preservation of the native cartilage and ligamentous attachments. Reconstruction of the diaphyseal defect with an intercalary allograft stabilized with an intermedullary nail through the centre of the physis allows continued growth at the physis. Incorporation of the allograft can be augmented by the addition of a vascularized fibula graft within the allograft. For tumours involving the distal femur or proximal tibia in young patients, an alternative option for reconstruction, preserving the foot, is an intercalary resection, and tibial turn-up (Van Nes) arthroplasty. The residual limb is rotated through 180o, the ankle joint now forming the novel knee joint. The resultant limb has the cosmetic appearance of an above knee amputation whilst allowing the capacity for longitudinal growth, if the proximal tibial physis has been preserved. Following rotationplasty, a prosthesis can be worn at the knee allowing ambulation. Gait analysis demonstrates improved kinematics when compared to a conventional above knee amputation. Careful consideration should be given not only to the technical demand of the procedure, but also the psychological impact on the patient and family of the disfiguring but highly functional procedure. The fact that the patients have no phantom pain is a distinct advantage over amputation at a similar level.

Non-Biological Reconstruction
Significant advances have been made in the design and manufacture of endoprostheses in the last 30 years. The advent of neo-adjuvant chemotherapeutic regimens has allowed an acceptable time lag between diagnosis and local control which allows for the manufacture of custom made endoprostheses based on the patients’ particular anatomy without delaying treatment. Primitive devices suffered from errors in manufacture resulting in implant fractures and early loosening with non-rotating knee prostheses. The current generation of endoprostheses offer an attractive life span for the majority, failure largely attributable to stress shielding in long stem endoprostheses and particle-induced osteolysis due to wear at the bearing interface. Failure is largely dependent on anatomical location, with proximal humeral and proximal femoral devices faring best, whilst distal femoral and proximal tibial prostheses perform less well. Patients with endoprostheses will undoubtedly require revision surgery within their lifetime, each time requiring greater osseous and soft tissue resection. The risk of infection remains high and increases with each revision procedure, leading, in the worst-case scenario, to possible amputation. This risk is increased when radiotherapy is employed, particularly for endoprosthetic reconstruction of the proximal tibia.
In younger patients, with more than 2 years of growth remaining, the issue of limb-length equalization is a real concern, particularly at the distal femur, where the physis here accounts for the majority of longitudinal growth. In such patients, “growing” prostheses present an attractive answer. Prostheses incorporating a growing distraction device can allow predictable lengthening and equalization of leg lengths. Minimally invasive growing prostheses (Fig. 4), where the device is lengthened by a distraction screw, accessed through a small incision, can be used in patients where surveillance of local recurrence is expected to require MRI. In those where local recurrence is unlikely, a non-invasive growing prosthesis (Fig. 5) can be employed. In such devices, the prosthesis incorporates a magnetic motor activated by an external rotating magnet applied in close proximity to the limb. This overcomes the need for repeated surgical procedures, and the inherent risk of infection this carries. However, patients with such devices cannot undergo further MRI scanning due to the irreparable damage this incurs on the magnetic motor. Whichever endoprosthetic device is chosen, consideration should be given to the method of fixation to native bone. The failures of early devices, attributable to particle-mediated osteolysis, have, to a certain extent, been obviated by the use of hydroxyapatite collars, essentially sealing the medullary canal and implant-bone interface from particulate wear generated at the bearing surface[53,54].

Conclusion 

The paucity of algorithms to guide treatment strategies in paediatric patients with osseous sarcomas is a reflection of the multifactorial influences that predict outcomes following resection. An appropriate strategy can only be achieved following careful consideration of oncological, pathological, surgical and patient factors. Whichever strategy is adopted, the sequence of priorities should always be first life, then limb, then function, with leg length discrepancy and cosmetic appearance affording lesser consideration. When true equipoise exists between limb salvage and limb sacrifice, in terms of overall and disease-free survival, consideration must be given to limb function not only in the immediate periods following reconstruction, but also for the entirety of the life of the patient. In the case of the paediatric population, this may exceed the professional lifetime of the treating surgeon.

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How to Cite this article: Parry M, Grimer R. Limb Salvage in Paediatric Bone Tumours. Journal of  Bone and Soft Tissue Tumors Sep-Dec 2015;1(2): 10-16.
M R

(Abstract)      (Full Text HTML)      (Download PDF)

Natural “Barriers” Its Relevance To The Spread Of Bone Sarcoma

Vol 1 | Issue 2 | Sep – Dec 2015 | page:5-9 | K C Gopalakrishnan[1]

Author: K C Gopalakrishnan[1].

[1] SUT Hospital, Pattom,Trivandrum,Kerala, India.

Address of Correspondence
Dr.K C Gopalakrishnan,M.S Ortho,M.Ch,
Senior Consultant and Head,Orthopedic Surgeon at SUT Hospital, Pattom,Trivandrum,Kerala, India.
Email: kcgopalakrishnan@hotmail.co.uk

Abstract

Cancer grows locally in a centrifugal manner and reaches distal sites via lymphatic and vascular pathways. It is unclear what provisions in the tumour prompt the migration pathway. In depth knowledge of human anatomy extrapolated with Common sense, guide and prompt us to think of the “Natural barriers” in the centrifugal spread of tumours.
Certain tissues in the limbs, such as articular cartilage ,synovium and capsule, thick cortical bone and periosteum, major fascias septae, tendon origin and insertion of muscles and in childhood thick physeal cartilage act as natural barriers. These structures, by virtue of their unique anatomy, act as “NATURAL BARRIERS” to tumour spread and separate tissues into distinct anatomical spaces called compartments.
Keywords: Bone sarcoma, paediatric tumors, natural barriers.

Introduction

Humans in their pursuit of achieving self-sufficiency in life, have conquered many mountains of success, many yet to climb. We, health professionals, have shared these success stories in understanding the causes and the right remedial means in many diseases humans suffer. At least a few of us might feel strange when we come to realise that cancer begins in one’s own cell; bone cancer for that matter is no exception. When sarcoma and cancer spread from its site of origin to the lungs, liver kidney, brain or cardiovascular system, the life ends, all on a sudden or insidiously.
A clear knowledge of tissues and structures which are normally present in our body and are recruited to perform the additional function of containing the noxious agent, like a sarcoma, from spreading is essential for any clinician dealing with bone tumors. In a global perceptive this is similar to the sea, mountains and rivers being used as territorial barriers of nations.

Clinical Relevance
This brief presentation is to provide an insight to the oncologic team responsible in the management of bone and soft tissue sarcoma on the following:-
a) Staging of tumour
b) Planning per cutaneous biopsy
c) Extent of work up needed for metastasis
d) Type of resection of the local lesion
e) Projecting the prognosis of a sarcoma.

Athorough knowledge of the anatomical spaces (compartments) into which malignant tumours extend from their site of origin is essential to stage the tumour and plan the steps of local surgical treatment. In this context what commonly referred as “Natural barriers “is relevant in the evaluation neoplastic growths, malignant tumours in particular.

Table 1
The primary goal of an oncologic surgeon is to provide local control of disease by obtaining adequate tumour margin at the time of resection. Today local disease control, where ever possible is achieved through a limb-sparing procedure, however, if the lesion is too advanced, an amputation or even disarticulation will be required for disease control. The decision to amputate or perform a limb sparing procedure depends on many factors. These include ,size of tumour, the relationship of tumour to adjacent structures such as nerves, blood vessels, involvement of adjacent joint and the overall stage of the tumour at presentation.

Fig 1 2 3
Although different staging systems now exist, it can be seen that they are all based on three common components; namely the grade of the tumour, its local extent and the presence of metastasis. The system of Enneking staging (1, 2 3) which has been adopted by MSTS is shown in table 1.
The grade of the tumour is a measure of its ability to metastasise. It is based on primarily on histologic features such as cellular atypia, number of mitoses, degree of necrosis and vascularity. A sarcoma is classified as either low- grade or high- grade. In general a low- grade lesion is less biologically active and will require a relatively conservative surgical procedure, conversely a high grade lesion will usually require a more radical procedure because of its more aggressive nature.

FIg 4 5 6
Factors related to the tumour site include the size of the lesion and its local extent. Sarcomas tend to grow centrifugal lay along pathways of least resistance and are contained in part by a pseudo capsule as they extend into adjacent tissues. Encapsulation is a reflexion of host response. In biologically active and in malignant tumours encapsulation is incomplete. A malignant lesion may remain contained within the pseudo capsule (intra-capsular) but in general malignant cells often extend beyond the capsular boundaries (skip lesions). If a lesion extends through its capsule but is still confined within a single anatomical compartment, it is considered extra-capsular but intra-compartental. If the tumour extend into an adjacent compartment it is classified as extra-compartmental. In general lesions with more advanced local extension including involvement of neurovascular structures or joint, require excision of more adjacent tissue than do smaller tumors that have not spread to local soft tissues. At time of diagnosis most bone sarcomas would have breached the bony cortex and spread to local soft tissue, making them bicompartmental. This may be specifically correct in our country where there is always a delay in diagnosis due to ignorance on part of patient or multiple consultations that are sought by the patients.
The third component of the staging system is the presence of lymph nodal or distant metastasis. Regional lymph node involvement is much less common with musculoskeletal sarcomas than are pulmonary metastasis, but both are equally poor prognostic factors.

Fig 7 8

Anatomic Compartments
Certain tissues in the limbs, such as articular cartilage, synovium and capsule, cortical bone and periosteum , major fascia’s septate, tendon origin and insertion of muscles, in childhood the wide physical cartilage, act as ” natural barriers” to tumour spread and separate tissues into distinct Anatomic Spaces called compartments .Among the natural barriers mentioned above, the physeal cartilage deserves special mention. In the pre-adolescent age the physeal cartilage in the lower femur and upper tibia is very wide. Between its second and third layers of the physeal cartilage (Fig. 1) there are no constant blood vessel demonstrated, also except at the subperiosteally region, no constant anastomoses between epiphyseal and metaphyseal vessels. This variation in blood supply of the physeal cartilage has a bearing on the spread of tumours in the metaphyseal region. Therefore a malignant lesion confined to the metaphyseal side of the physeal cartilage can be considered for radical removal through the second and third layer as extracompartmental resection. On a personal experience ,Intercalary resection for osteosarcoma with over twenty five years of follow up have confirmed wide physeal cartilage in the lower femur and upper tibia is a predictable natural barrier (Fig. 2 ). The greatest advantage of this type of resection is, it is radical, and ECRT of resected bone and reconstruction with the same bone becomes anatomical. If goes uncomplicated the reconstruction becomes biological, function will be excellent and cosmetically normal and lifelong.
A tumour confined to one of these spaces is considered intra-compartental and is of a lower stage than a lesion that has spread beyond these barriers classified as extra- compartmental. This extra-compartmental spread may occur via direct tumour invasion of an adjacent space or by contamination resulting from fracture (Fig. 3) haemorrhage or an operative procedure such as an unplanned resection or an inadvertently planned biopsy. An extra- compartmental lesion will require a more radical resection than one that is purely intra-compartmental.
Fat areoles tissue and muscle are relatively poor natural barriers to spread of tumours and certain regions in the body that are composed of these tissues are considered completely extra compartmental. A tumour involving any of these regions whether it arose there or involved from adjacent compartments is considered extra- compartmental.
An update on the anatomic spaces (compartments) of the extremity is briefly described. Without that a presentation on natural barriers of malignant tumour spread would be incomplete.

Skin And Subcutaneous Fat
The skin and subcutaneous fat together are considered a single compartment. They are separated from deeper tissues by a thick fascia, deep fascia,. There are no barrier for longitudinal spread of tumour in this compartment.

Bone
Each bone is considered an individual compartment bounded by the cortex and periosteum and the articular cartilage at the ends. A purely intraosseous lesion is therefore considered intracompartmental (Fig. 4), whereas tumour extending from bone to adjacent soft tissue (Fig. 5) or vice versa would be considered extra-compartmental.

Paraosseous
Except at the site of attachment of muscles there is a narrow space occupied by areolar tissue around large bones like humerus, femur and tibia. This space between the bone and overlying tissue is considered a compartment because a lesion could arise in that location without invading bone or adjacent soft tissues.

Intra Articular
Each joint is considered a distinct compartment bounded by synovial and capsular tissues.

Muscle
A tumour confined to a single muscle is considered intra-compartmental. However extension of tumour beyond the muscle is still considered intra-compartmental if it is confined to a larger compartment bounded by natural barriers such as fascia or tendon

Nerves And Blood Vessels
Neurovascular structures are not classically considered compartments but must be evaluated during staging or biopsy of sarcoma. Tumour spread usually occur between compartments along neurovascular bundles and involvement of major nerves may preclude the possibility of limb sparing procedure.

Upper Extremity
Periscapular: – The muscles and fasciae covering the dorsal scapula are considered a compartment. They include the infraspinatus, trees minor and rhomboid muscles. The supraspinatus muscle is in a separate compartment, as the spine of the scapula separate these two regions.
Upper arm: – The soft tissues of the upper arm are divided into two compartments: anterior and posterior (Fig. 6) the anterior compartment contains the biceps, brachialis, coracobrachialis and brachioradialis muscle. The triceps musculature comprises the posterior compartment.
Forearm: – The forearm contains two compartments: dorsal and volar (Fig. 6).The extensor muscles in the dorsal compartment; it is separated from the volar compartment by the interosseous membrane. The flexor muscles are found in the volar compartment.
Hand: – The palmar soft tissues are separated into multiple compartments but because they are so compact and have so many neurovascular communications, most lesions involving this region are considered extra-compartmental.
Extra-compartmental spaces of the upper extremity: – Purely extra-compartmental spaces of the upper extremity include the periclavicular region, axilla, antecubital fossa, wrist and the dorsum of the hand.

Pelvis
A lesion confined to a single bone or muscle within the pelvis would be considered intra-compartmental, but most lesions are large at presentation and show extra-compartmental spread to adjacent tissues by the time the patient is examined.

Lower Extremity
Thigh :- Three compartments make up the thigh anterior, posterior and medial(Fig. 7) The anterior compartment contains the iliotibial tract and tensor muscle of the fascia lata and the quadriceps musculature (rectus femoris, vastus medialis, vastus lateralis, vastus intermedius) the vastus intermidius muscle is sometimes considered a separate , fourth compartment. The posterior compartment contains the hamstring muscles (semimembranosus, semitendinosus and biceps femoris) as well as sciatic nerve. The gracilis and adductor muscles lie within the medial compartment. Although the sartorius muscle is an anterior structure proximally and a medial structure in the distal thigh, it is classically considered an anterior compartment structure.
Lower leg: – The lower leg is divided into four compartments. Anterior, deep posterior, superficial posterior, and lateral (Fig. 8). The anterior compartment contains the tibialis anterior, extensor digitorum long is, and extensor hallusis logus muscles as well as the anterior tibial vessels and deep peroneal nerve. The anterior compartment is separated from the deep posterior compartment by the interosseous membrane. The tibialis posterior, flexor digitorum, flexor hallucis longus muscles lie in the deep posterior compartment along with the posterior tibial and peroneal arteries and the posterior tibial nerve. The superficial posterior compartment contains the gastrocnemius and soleus muscles and the sural nerve. The peroneal muscles lie in the lateral compartment along with common and superficial peroneal nerves.
Foot: – The plantar tissues of the foot are divided into three compartments: medial central and lateral. The medial compartment contains the abductor hallucis and flexor hallucis brevis muscles. The flexor digitorum brevis, quadratus plantae, lumbricals and adductor hallucis muscles lie in the central compartment. The lateral compartment contains the abductor and short flexor muscles.
Extra-compartmental spaces in the lower extremity. The groin (inguinal region and femoral triangle) popliteal fossa ankle and dorsum of foot are considered extra-compartmental.

Principles Of Percutaneous Biopsy
Choose the shortest route from skin and the lesion.
Avoid neurovascular and joint, lung, bowel, and other organs.
In suspected malignant lesions the needle path to be in the line of incision for resection.
The needle should not traverse an uninvolved compartment.
Osseous tumours, like Osteosarcoma, most commonly affect the proximal humerus, pelvis, distal femur and proximal tibia. Safe Per cutaneous biopsy approach is described below.
The pre-treatment work up in a suspected musculoskeletal sarcoma should include plain radiograph, ultra sound scan, CT scan of local and chest, pre and post chemotherapy MRI of lesion, bone scan and in selected patients PET scan(4, 5).

Proximal Humerus
Lesions in this region should be biopsied using an anterior approach through the anterior third of the deltoid muscle. The deltoid muscle is innervated by the axillary nerve from posterior to anterior. If needle track is chosen anywhere in the posterior two thirds of the muscle, the residual anterior portion will be essentially denervated and functionless after resection of the posterior portion of the muscle.

Pelvis
A needle path through the gluteal muscles should be avoided for lesions in the pelvis because resection of these muscles during a limb sparing procedure will result in poor functional outcome. An anterior approach preferably through the anterior superior iliac spine or anterior inferior iliac spines spines should be used wherever possible. The posterior superior iliac spine is an alternative route.

Distal Femur
An anterior approach through the rectus femoris or quadriceps tendon should be avoided. If the quadriceps tendon must be resected as part of a limb sparing procedure because the biopsy passed through it, the functional result is suboptimal. A medial or lateral needle path can be used for lesions in this region, though a medial surgical approach affords optimal access to the neurovascular structures during resection.

Proximal Tibia
An anteromedial approach should be used for tumours in the proximal tibia because it will avoid contaminating adjacent compartments.

For an orthoapedic oncology surgeon there is always a tussle between removing all the affected tissue while preserving all normal tissue. For this reason anatomical landmarks and detailed knowledge of compartments is much more important to an orthopaedic oncology surgeon. Again the same knowledge will be needed by faculties of interventional radiology and pathologist too. In this review, I have tried to cover the most important clinical principles along with anatomical details of common sites. however this review is by no means exhaustive and a more detailed knowledge should be acquired from other sources and articles.

Conclusion

Anatomical boundaries play crucial role in limiting spread of sarcomas. A thorough knowledge of the anatomical spaces (compartments) which are bounded by natural barriers is essential for staging of tumours.  The management plan will alters depending on the integrity of these natural barriers. This knowledge is also essential in performing per cutaneous needle biopsy and limb sparing resection procedures.

References

1 . Enneking WF, Spanier SS, Goodman MA. A system for the surgical staging of Musculoskeletal sarcoma. Clin. Orthop Relat Res 1980; 153; 106-120.
2. Enneking WF, Spannier SS, Goodman MA. A System for the surgical staging of Musculoskeletal sarcoma, 1980 Clin Orthop Relat Res, 2003; 415:4-18.
3. M.U .Jawad, S.P.Scully: Enneking Classification: Benign and Malignant Tumours Of the Musculoskeletal System. Clin Orthop Relat Res 2010’468:2000-2002.
4. Olson PN, Everson Ll Griffiths Hj, staging of musculoskeletal tumours. Radiological Clin North Americaa1994’32 ,151-162.
5. Sundaram M, Mc Guire MH, Herbold DR, Wolverson MK,Heiberg E: Magnetic resonance imaging in planning Limb Salvage Surgery for primary malignant tumours of bone. JBJS A ,1986 ,68A,809-819.

How to Cite this article: K C Gopalakrishnan. Natural “Barriers” Its Relevance To The Spread Of Bone Sarcoma. Journal of  Bone and Soft Tissue Tumors Sep-Dec 2015;1(2): 5-9.
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Paediatric Bone Tumours

Vol 1 | Issue 2 |  Sep- Dec 2015 | page:3 | Dr Subin Sugath.

Author: Dr Subin Sugath [1].

[1]Orthopaedic Oncology Clinic, Pune, India.
[2] Indian Orthopaedic Research Group, Thane, India
[3] Sancheti Institute for Orthopaedics &Rehabilitation, Pune, India

Address of Correspondence
Dr. Subin Sugath MS Orth.
Department of Ortho Oncology.
Aster DM Healthcare Pvt Ltd. Kuttisahib Road, Near Kothad
Bridge, South Chittoor PO, Cheranallor, Kochi 682 027,
Kerala, India.
Email: drsubin.sugath@dmhealthcare.com

Paediatric Bone Tumours

Bone tumours are rare as they constitute less than 2% of all malignancies. Though they can affect any age group, paediatric age group forms one of the commonest subsets affected by this. Osteosarcoma and Ewings Sarcoma, two common primary malignant bone tumours are commonly seen in patients less than 20 years of age. Since Ewings sarcoma was discussed in details in the last issue of the journal, the present symposium tries to cover certain general aspects of paediatric bone tumors in some details rather than discussing individual tumors. The outcome of treatment of this malignancy has seen a drastic improvement with the use of more potent chemotherapeutic drugs, newer imaging modalities which tell you the exact extent of these tumours and improved surgical techniques. The overall survival and disease free survival have increased from the dismal levels prevalent in the eighties to promising new levels. Amputation which was the choice of treatment earlier has been replaced by limb preserving surgeries where only the diseased bone is removed rather than the entire affected limb. An adult and a paediatric patient cannot be equated when it comes to management of bone tumours. The challenges in treating a child with bone tumour are more considering the age, size of the patient and bone, the remaining growth potential and the difficulty in using conventional reconstruction options after tumour resection. An open physis can be considered as a thick barrier to tumour spread and can be taken as a margin while doing tumour resection in children. The concept of margin and their implications in tumour surgery in children has been discussed in the article by Prof. K.C Gopalakrishnan [1]. The article is written from a surgical anatomy/pathology point of view and will be very helpful in understanding the basic of natural barriers and spread of tumors. Conventional reconstruction technique using prosthesis causes limb length discrepancy at the time of skeletal maturity as the unoperated limb grows normally while the operated limb doesn’t as the growth plate is also removed during the tumour excision. Different reconstruction options which can overcome this are discussed in detail in the article by Prof. Robert Grimer [2]. The decision making between limb sacrifice and limb salvage is difficult one both for the patient and for the surgeon. Factors like life span, limb function, patient’s wishes and expected limb function will help guiding the decision. At times, this decision may be quite difficult and may challenge even a lifetime experience of an orthopaedic oncology surgeon [2]. Expandable implants which can be lengthened over a period of time to compensate for the growth of the contralateral limb has come a long way in making prosthetic replacement an acceptable option in children with bone tumours. Various biological methods of reconstruction using autografts and allografts have their own advantages as it can be a lifelong solution once they incorporate with the host bone. Reimplantation of the tumour bone after sterilisation is also now accepted as a reconstruction option in children. Intercalary resections where the natural joints can be preserved require precise surgical resections to attain both oncological clearance and also to have a viable reconstruction option. Computer Assisted Orthopaedic Surgery (CAOS) has come a long way in helping to attain this goal. The benefits of this technique are explained in the article by Prof. Lee Jeys where he also discusses the use of CAOS in complex pelvic surgeries [3]. The benefits of using high dose methotrexate has been debated for long. Although methotrexate is been use since 1960’s, the currently literature still does not have enough evidence to recommend for or against its use. Some studies have shown strong positive effect while others have shown no advantage. The use of high dose methotrexate based chemotherapy has been outlined in the article by Dr Vivek Radhakrishnan [4]. They have also tried to review the important existing literature and provide recommendation for use of high dose methotrexate in paediatric osteosarcomas. Applicability of high dose methotrexate is also discussed in the Indian scenario and this may be applicable to most developing world countries.  In all keeping up with the multidisciplinary approach discussed in the editorial [5], the current symposium has tried to present anatomical/pathological, surgical and medical aspect of bone tumors along with recent advances in the field. Children with bone tumours need to be treated differently from adults while considering the management and I hope these series of articles will help to enlighten us in the management of these complex problems.

Dr Subin Sugath

References
1. K C Gopalakrishnan. Natural “Barriers” Its Relevance To The Spread Of Bone Sarcoma. Journal of Bone and Soft Tissue Tumors Sep-Dec 2015;1(1):5-9.
2. Parry M, Grimer R. Limb Salvage in Paediatric Bone Tumours. Journal of Bone and Soft Tissue Tumors Sep-Dec 2015;1(2):10-16.
3. Archer JE, May PL, Jeys LM. CAOS in Paediatric Bone Tumour Surgery. Journal of Bone and Soft Tissue Tumors Sep-Dec 2015;1(1):17-21.
4. Reghu K S, Radhakrishnan V S. High dose Methotrexate in Paediatric Osteosarcoma – a brief overview. Journal of Bone and Soft Tissue Tumors Sep-Dec 2015;1(1):22-24.
5. Panchwagh Y, Shyam AK. M.D.T. (Multi Disciplinary Team) For Sarcomas: A Must ! Journal of Bone and Soft Tissue Tumors Sept- Dec 2015; 1(2):1-2.

How to Cite this article: Sugath S. Paediatric Bone Tumours. Journal of  Bone and Soft Tissue Tumors Sep-Dec 2015; 1(2): 3-4.
Dr.Subin Sugath

         Dr.Subin Sugath

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M.D.T. (Multi Disciplinary Team) For Sarcomas: A Must !

 

Journal of Bone and Soft Tissue Tumors

Journal of Bone and Soft Tissue Tumors

Vol 1 | Issue 2 |  Sep- Dec 2015 | page:1-2 | Dr. Yogesh Panchwagh & Dr. Ashok Shyam.

Author: Dr. Yogesh Panchwagh [1], Dr. Ashok Shyam [2,3].

[1]Orthopaedic Oncology Clinic, Pune, India.
[2] Indian Orthopaedic Research Group, Thane, India
[3] Sancheti Institute for Orthopaedics &Rehabilitation, Pune, India

Address of Correspondence
Dr. Yogesh Panchwagh.
Orthopaedic Oncology Clinic, 101, Vasanth plot 29, Bharat Kunj Society -2, Erandwana, Pune – 38, India.
Email: drpanchwagh@gmail.com

Editorial: M.D.T. (Multi Disciplinary Team) For Sarcomas: A Must ! 

“Coming together is beginning, keeping together is progress, working together is success”: Henry Ford.

Henry Fords quote can be aptly extrapolated to the clinicians working in the field of orthopaedic oncology. Many a time, it is seen that interaction between various specialties is of paramount importance to reach to a logical conclusion while dealing with bone and soft tissue tumors. The rarity of these lesions and often-encountered complex clinical scenarios makes it mandatory for the treating clinicians to sit together to decide the diagnosis and further line of management. The multi disciplinary team (M.D.T.) that thus ensues is the key to success in management of bone and soft tissue tumors.
A typical M.D.T. comprises of (but may not be limited to) the sarcoma surgeons, medical and radiation oncologists, Pathologists, radiologists, Palliative care and rehabilitation specialists. It is expected that the institute where the M.D.T. is located should have reasonable experience in managing sarcoma patients. This number may vary from country to country. For example, In the U.K., it is expected that such an M.D.T. should be seeing at least 100 new soft tissue sarcoma cases every year or 25 primary bone sarcoma cases every year [1,3].
It is expected that all cases or suspected cases of sarcomas should have a speedy access to diagnosis and treatment. All diagnosed cases also need to be reviewed by a specialist in the M.D.T. The surgical management including the initial biopsy and definitive resection, chemotherapy and radiotherapy are to be carried out by member of a sarcoma MDT. In case that a surgeon who is a M.D.T. member is not available, the surgery should be done by a surgeon with tumor site-specific or age-appropriate skills, in consultation with the sarcoma MDT. Informing patients about relevant clinical trials and support to enroll into the trials as appropriate also forms a responsibility of the M.D.T [1,2,3,4].
Such MDT’s should be developed at individual centers that specialize in management of sarcomas. The advantages of such MDT approach is manifold. First it will allow complete and detailed assessment of patient and the disease at single center which will help in early and accurate diagnosis of the disease and extent of the disease. It will also help in more precise planning of management strategies and much better patient care. Sarcomas are unique diseases in the sense that they invoke a great sense of anxiety in the patients and their caregivers. These diseases have strong emotional responses and many a times lot of confusion exists in minds of the affected. In our country this leads to a varied response which many a times includes patient being referred and consulted by many doctors and surgeons before reaching a proper channel of care. A single coordinated MDT will help the patients to reach this channel much earlier. A coordinated approach at single center will help curb the patient’s and caregivers anxieties to a large extent and will also be much more convenient to them. The Australian Sarcoma Study Group have gone through the literature and produced evidence supporting MDT approach through following conclusions [1,2,3] :
1. MDT: Treatment at a dedicated MDT center results in better patient survival, decreased amputation risk, better chances of disease free survival. Also MDT center follow the clinical practice guidelines and have appropriate use of preoperative imaging and biopsy.
2. Supportive care: This is one of the most important aspect of patient care that help in providing better care for the patient as a whole. It helps in improving the quality of life, patients stay fewer days in the hospital, require fewer home visits and have better physical, social and emotional responses.
3. In MDT scenario the expert panel of radiologist will be able to diagnose the disease early and also pathological diagnosis is much more accurate in MDT settings.
There have been some attempt to bring together various specialties in our country too. Specifically there have been common forum and meetings where specialties have come together to share their views. Few centers have regular interspeciality meetings too. The Indian Musculoskeletal Oncology Society has organized a multifaculty meeting in Pune in October 2015 and hopefully they will continue to foster this development. Centers that specialize in sarcoma care should realize the importance of MDT approach. Although specialized centers do have coordinated approach, a more formal MDT body will help make the system more organized and effective. Journal of Bone and Soft Tissue supports the multidisciplinary approach and the first issue had authors from almost all specialist involve in sarcoma care. We wish to involve more specialties and specialist involved in sarcoma care with JBST and in coming issues our focus will be to publish articles with more coordinated approach to oncology care.
The MDT approach has been successfully used in many countries. In fact the U.S. National Cancer Control Network (NCCN) (www.nccn.org) and the U.K.s National Institute for Health and Clinical Excellence (NICE) (www.nice.org.uk) both have detailed recommendation for use of MDT approach in management of sarcomas. The developing countries too need to follow a similar model in the interests of the sarcoma patients. It is still not very uncommon in a country like India, which dreams of a digital revolution, to see examples of late diagnosis, improper biopsies, incorrect interventions and non-evidence based management. We believe that there is a need to prepare our own guidelines, modified according to suit the geography, disease prevalence and health care and infrastructural capabilities and to promote the concept of MDT in the care of sarcomas.

Yogesh Panchwagh & Ashok Shyam

References

1. National Institute for Health and Clinical Excellence, 2006. Improving outcomes for people with sarcoma. NICE guidance on cancer services.
2. Robert Grimer Nick Athanasou, Craig Gerrand, Ian Judson, Ian Lewis, Bruce Morland, David Peake, Beatrice Seddon, and Jeremy Whelan. 
UK Guidelines for the Management of Bone Sarcomas. 
Sarcoma. 2010; 2010: 317462.
3. Why Multi disciplinary care is important in sarcomas. www.australiansarcomagroup.org/multi-disciplinary-care.html
4. The ESMO / European Sarcoma Network Working Group. Bone Sarcomas: ESMO Clinical Practice Guidelines. Ann Oncol (2014) 25 (suppl 3): iii113-iii123.

How to Cite this article: Panchwagh Y, Shyam AK. M.D.T. (Multi Disciplinary Team) For Sarcomas: A Must !  Journal of  Bone and Soft Tissue Tumors Sept-Dec 2015; 1(2):1-2.

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